WO2000052134A2 - Inhibitors of prenyl-protein transferase - Google Patents
Inhibitors of prenyl-protein transferase Download PDFInfo
- Publication number
- WO2000052134A2 WO2000052134A2 PCT/US2000/005215 US0005215W WO0052134A2 WO 2000052134 A2 WO2000052134 A2 WO 2000052134A2 US 0005215 W US0005215 W US 0005215W WO 0052134 A2 WO0052134 A2 WO 0052134A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- substituted
- alkyl
- aryl
- cycloalkyl
- heterocycle
- Prior art date
Links
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- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
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- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
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- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
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- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- R ⁇ , R3 and R ⁇ are optionally attached to the same carbon atom;
- R! 1 is independently selected from C]-C6 alkyl and aryl
- V is selected from: a) hydrogen, b) heterocycle selected from pyrrolidinyl, imidazolyl, pyridinyl, thiazolyl, pyridonyl, 2-oxopiperidinyl, indolyl, quinolinyl, isoquinolinyl, and thienyl, c) aryl, d) C1-C2O alkyl wherein from 0 to 4 carbon atoms are replaced with a heteroatom selected from O, S, and N, and e) C2-C2O alkenyl, and provided that V is not hydrogen if A ⁇ is S(O) m and V is not hydrogen if A* is a bond, n is 0 and A 2 is S(O) m ;
- R a is selected from: Ci-4 alkyl or C3-6 cycloalkyl, unsubstituted or substituted with: a) C 1-4 alkoxy, b) halogen, or c) aryl or heterocycle;
- R8 is independently selected from: a) hydrogen, b) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, Rl°O-, R! °C(O)NR 1 0 -, CN, NO2, (R 10 )2N-C(NRl°)-, Rl°C(O)-, -N(R1°)2, or RH0C(0)NR1 °-, and c) C l -C ⁇ alkyl substituted by C i -C ⁇ perfluoroalkyl, R!
- the ratio of the EC 50 of the compounds of this second embodiment of the instant invention for inhibition of the cellular processing of the hDJ protein (Example 22) to the EC 50 of the compounds of the instant invention for inhibition of the cellular processing of the Rapl protein is between about 1 and about 100.
- aryl is intended to mean any stable monocyclic or bicyclic carbon ring of up to 7 members in each ring, wherein at least one ring is aromatic.
- aryl elements include phenyl, naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl, anthryl or acenaphthyl.
- heterocycle or heterocyclic represents a stable 5- to 7-membered monocyclic or stable 8- to 11-membered bicyclic heterocyclic ring which is either saturated or unsaturated, and which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O, and S, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring.
- heterocycle or heterocyclic includes heteroaryl moieties.
- the heterocyclic ring may be attached at any heteroatom or carbon atom which results in the creation of a stable structure.
- heterocyclic elements include, but are not limited to, azepinyl, benzimidazolyl, benzisoxazolyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, cinnolinyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl sulfone, furyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isochromanyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, isothiazolidinyl, morpholinyl, naphthyridinyl, oxadiazolyl,
- R 4 is hydrogen
- a water soluble taste masking material such as hydroxypropylmethyl-cellulose or hydroxypropylcellulose, or a time delay material such as ethyl cellulose, cellulose acetate buryrate may be employed.
- Formulations for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water soluble carrier such as polyethyleneglycol or an oil medium, for example peanut oil, liquid paraffin, or olive oil.
- the compounds of the instant invention may also be, co- administered with other well known therapeutic agents that are selected for their particular usefulness against the condition that is being treated.
- the compounds of the instant invention may also be co-administered with other well known cancer therapeutic agents that are selected for their particular usefulness against the condition that is being treated. Included in such combinations of therapeutic agents are combinations of the instant farnesyl-protein transferase inhibitors and an antineoplastic agent. It is also understood that such a combination of antineoplastic agent and inhibitor of farnesyl-protein transferase may be used in conjunction with other methods of treating cancer and/or tumors, including radiation therapy and surgery.
- the preferred class of antineoplastic agents is the taxanes and the preferred antineoplastic agent is paclitaxel.
- a IL flask with cooling/heating jacket and glass stirrer (Lab-Max) was charged with water (200 mL) at 25°C.
- the thioimidazole (90.27 g), as described in Step 2 was added, followed by acetic acid (120 mL) and water (50 mL) to form a pale pink slurry.
- the reaction was warmed to 40°C over 10 minutes.
- Hydrogen peroxide (90.0 g) was added slowly over 2 hours by automatic pump maintaining a temperature of 35-45 °C. The temperature was lowered to 25°C and the solution aged for 1 hour.
- the solution was cooled to 20°C and quenched by slowly adding 20% aqueous Na2SO3 (25 mL) maintaining the temperature at less than 25°C.
- the solution was filtered through a bed of DARCO G-60 (9.0 g) over a bed of SolkaFlok (1.9 g) in a sintered glass funnel. The bed was washed with 25
- the modified geranylgeranyl-protein transferase inhibition assay is carried out at room temperature.
- a typical reaction contains (in a final volume of 50 ⁇ L): [3H]geranylgeranyl diphosphate, biotinylated Ras peptide, 50 mM HEPES, pH
- the cells are labeled in 3 ml methionine-free DMEM supplemented with 10% regular DMEM, 2% fetal bovine serum and 400 ⁇ Ci[35s]methionine (1000 Ci/mmol).
- the cells are lysed in 1 ml lysis buffer (1% NP40/20 mM HEPES, pH 7.5/5 mM MgCl2/lmM DTT/10 mg/ml aprotinen/2 mg/ml leupeptin/2 mg/ml antipain/0.5 mM PMSF) and the lysates cleared by centrifugation at 100,000 x g for 45 min.
- Sense strand C-terminal SEAP 5' GAGAGAGTCTAGAGTTAACCCGTGGTCC CCGCGTTGCTTCCT 3' (SEQ.ID.NO.:5)
- An expression plasmid constitutively expressing the SEAP protein was created by placing the sequence encoding a tmncated SEAP gene downstream of the cytomegalovirus (CMV) IE-1 promoter.
- the expression plasmid also includes the CMV intron A region 5' to the SEAP gene as well as the 3' untranslated region of the bovine growth hormone gene 3' to the SEAP gene.
- the sense strand oligo optimizes the 'Kozak' sequence and adds an
- the human c-H-ras gene can be PCRed from a human cerebral cortex cDNA library (Clontech) using the following oligonucleotide primers.
- PSN-1 human pancreatic carcinoma
- viral-K4B-ras-transformed Ratl cells are used for analysis of protein processing.
- Subconfluent cells in 100 mm dishes are fed with 3.5 ml of media (methionine-free RPMI supplemented with 2% fetal bovine semm or cysteine-free/methionine-free DMEM supplemented with 0.035 ml of 200 mM glutamine (Gibco), 2% fetal bovine semm, respectively) containing the desired concentration of test compound, lovastatin or solvent alone.
- media methionine-free RPMI supplemented with 2% fetal bovine semm or cysteine-free/methionine-free DMEM supplemented with 0.035 ml of 200 mM glutamine (Gibco), 2% fetal bovine semm, respectively
- the supernatant is added to 1 ml of Dilution Buffer 0.1% Triton X- 100, 5 mM EDTA, 50 mM NaCl, 10 mM Tris pH 1.4) with 2 ⁇ g Kirsten-ras specific monoclonal antibody, c-K-ras Ab-1 (Calbiochem).
- the second protein/antibody mixture is incubated on ice at 4°C for 1-2 hours.
- the immune complex is collected on pansorbin (Calbiochem) coated with rabbit antisemm to rat IgG (Cappel) by tumbling at 4°C for 45 minutes.
- Rapl is eluted from the beads by heating at 95°C for 5 minutes, after which the beads are pelleted by brief centrifugation. The supernatant is subjected to SDS-PAGE on a 12% acrylamide gel (bis-acrylamide: acrylamide, 1 :100), and the Rapl visualized by fluorography.
- PSN-1 cells are passaged every 3-4 days in 10cm plates, splitting near- confluent plates 1 :20 and 1 :40.
- the day before the assay is set up 5x 10 cells are plated on 15cm plates to ensure the same stage of confluency in each assay.
- the media for these cells is RPM1 1640 (Gibco), with 15%> fetal bovine semm and lx Pen/Strep antibiotic mix.
- the day of the assay cells are collected from the 15cm plates by trypsinization and diluted to 400,000 cells/ml in media. 0.5ml of these diluted cells are added to each well of 24-well plates, for a final cell number of 200,000 per well. The cells are then grown at 37°C overnight.
- the compounds to be assayed are diluted in DMSO in
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Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU33866/00A AU3386600A (en) | 1999-03-03 | 2000-03-01 | Inhibitors of prenyl-protein transferase |
CA002363169A CA2363169A1 (en) | 1999-03-03 | 2000-03-01 | Inhibitors of prenyl-protein transferase |
EP00912071A EP1158982A4 (en) | 1999-03-03 | 2000-03-01 | Inhibitors of prenyl-protein transferase |
JP2000602746A JP2003524618A (en) | 1999-03-03 | 2000-03-01 | Prenyl protein transferase inhibitors |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12296899P | 1999-03-03 | 1999-03-03 | |
US60/122,968 | 1999-03-03 | ||
US12713299P | 1999-03-31 | 1999-03-31 | |
US60/127,132 | 1999-03-31 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2000052134A2 true WO2000052134A2 (en) | 2000-09-08 |
WO2000052134A3 WO2000052134A3 (en) | 2001-07-05 |
Family
ID=26821066
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/005215 WO2000052134A2 (en) | 1999-03-03 | 2000-03-01 | Inhibitors of prenyl-protein transferase |
Country Status (6)
Country | Link |
---|---|
US (1) | US6376496B1 (en) |
EP (1) | EP1158982A4 (en) |
JP (1) | JP2003524618A (en) |
AU (1) | AU3386600A (en) |
CA (1) | CA2363169A1 (en) |
WO (1) | WO2000052134A2 (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005028427A1 (en) * | 2003-09-22 | 2005-03-31 | F. Hoffmann-La Roche Ag | Aminoalkylamide substituted cyclohexyl derivatives |
US8431575B2 (en) | 2010-02-18 | 2013-04-30 | Transtech Pharma, Inc. | Phenyl-heteroaryl derivatives and methods of use thereof |
US9278917B2 (en) | 2012-05-17 | 2016-03-08 | Genentech, Inc. | Process for making amino acid compounds |
US9290458B2 (en) | 2012-05-17 | 2016-03-22 | Genentech, Inc. | Amorphous form of an AKT inhibiting pyrimidinyl-cyclopentane compound, compositions and methods thereof |
US9309204B2 (en) | 2012-05-17 | 2016-04-12 | Array Biopharma Inc. | Process for making hydroxylated cyclopentylpyrimidine compounds |
US9315471B2 (en) | 2012-05-17 | 2016-04-19 | Genetech, Inc. | Process of making hydroxylated cyclopentapyrimidine compounds and salts thereof |
US9416110B2 (en) | 2012-05-17 | 2016-08-16 | Array Biopharma Inc. | Process for making hydroxylated cyclopentylpyrimidine compounds |
US9452990B2 (en) | 2012-06-20 | 2016-09-27 | Novartis Ag | Complement pathway modulators and uses thereof |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7517890B2 (en) | 2003-11-20 | 2009-04-14 | Children's Hospital Medical Center | GTPase inhibitors and methods of use |
WO2007016539A2 (en) | 2005-07-29 | 2007-02-08 | Children's Hospital Medical Center | Gtpase inhibitors and methods of use and crystal structure of rac-1 gtpase |
NZ604035A (en) | 2010-06-04 | 2015-02-27 | Albany Molecular Res Inc | Glycine transporter-1 inhibitors, methods of making them, and uses thereof |
WO2013166043A1 (en) | 2012-05-02 | 2013-11-07 | Children's Hospital Medical Center | Rejuvenation of precursor cells |
US10028503B2 (en) | 2014-06-18 | 2018-07-24 | Children's Hospital Medical Center | Platelet storage methods and compositions for same |
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US4150052A (en) * | 1971-02-04 | 1979-04-17 | Wilkinson Sword Limited | N-substituted paramenthane carboxamides |
US5972942A (en) * | 1997-03-27 | 1999-10-26 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
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JPH0710620B2 (en) | 1985-03-28 | 1995-02-08 | 株式会社リコー | Two-color thermosensitive recording label |
US4829065A (en) | 1987-04-24 | 1989-05-09 | Syntex Pharmaceuticals, Ltd. | Substituted imidazolyl-alkyl-piperazine and -diazepine derivatives |
US5219856A (en) | 1992-04-06 | 1993-06-15 | E. I. Du Pont De Nemours And Company | Angiotensin-II receptor blocking, heterocycle substituted imidazoles |
US5478934A (en) | 1994-11-23 | 1995-12-26 | Yuan; Jun | Certain 1-substituted aminomethyl imidazole and pyrrole derivatives: novel dopamine receptor subtype specific ligands |
US5856326A (en) | 1995-03-29 | 1999-01-05 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
IL117580A0 (en) * | 1995-03-29 | 1996-07-23 | Merck & Co Inc | Inhibitors of farnesyl-protein transferase and pharmaceutical compositions containing them |
AU5432696A (en) | 1995-04-07 | 1996-10-23 | Pharmacopeia, Inc. | Carbonyl-piperazinyl and piperidinil compounds which inhibit farnesyl protein transferase |
US6011029A (en) * | 1996-02-26 | 2000-01-04 | Bristol-Myers Squibb Company | Inhibitors of farnesyl protein transferase |
AU706495B2 (en) | 1996-04-03 | 1999-06-17 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
AU741725B2 (en) | 1997-08-27 | 2001-12-06 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
-
2000
- 2000-03-01 EP EP00912071A patent/EP1158982A4/en not_active Withdrawn
- 2000-03-01 US US09/516,756 patent/US6376496B1/en not_active Expired - Fee Related
- 2000-03-01 WO PCT/US2000/005215 patent/WO2000052134A2/en not_active Application Discontinuation
- 2000-03-01 JP JP2000602746A patent/JP2003524618A/en not_active Withdrawn
- 2000-03-01 AU AU33866/00A patent/AU3386600A/en not_active Abandoned
- 2000-03-01 CA CA002363169A patent/CA2363169A1/en not_active Abandoned
Patent Citations (2)
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US4150052A (en) * | 1971-02-04 | 1979-04-17 | Wilkinson Sword Limited | N-substituted paramenthane carboxamides |
US5972942A (en) * | 1997-03-27 | 1999-10-26 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
Non-Patent Citations (1)
Title |
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See also references of EP1158982A2 * |
Cited By (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005028427A1 (en) * | 2003-09-22 | 2005-03-31 | F. Hoffmann-La Roche Ag | Aminoalkylamide substituted cyclohexyl derivatives |
KR100806603B1 (en) * | 2003-09-22 | 2008-02-29 | 에프. 호프만-라 로슈 아게 | Aminoalkylamide substituted cyclohexyl derivatives |
CN100402495C (en) * | 2003-09-22 | 2008-07-16 | 弗·哈夫曼-拉罗切有限公司 | Aminoalkylamide substituted cyclohexyl derivatives |
US7442791B2 (en) | 2003-09-22 | 2008-10-28 | Hoffmann-La Roche Inc. | Aminoalkylamide substituted cyclohexyl derivatives |
US8431575B2 (en) | 2010-02-18 | 2013-04-30 | Transtech Pharma, Inc. | Phenyl-heteroaryl derivatives and methods of use thereof |
US8741900B2 (en) | 2010-02-18 | 2014-06-03 | Transtech Pharma, Llc | Phenyl-heteroaryl derivatives and methods of use thereof |
US9045461B2 (en) | 2010-02-18 | 2015-06-02 | Transtech Pharma, Llc | Phenyl-heteroaryl derivatives and methods of use thereof |
US9290458B2 (en) | 2012-05-17 | 2016-03-22 | Genentech, Inc. | Amorphous form of an AKT inhibiting pyrimidinyl-cyclopentane compound, compositions and methods thereof |
US9278917B2 (en) | 2012-05-17 | 2016-03-08 | Genentech, Inc. | Process for making amino acid compounds |
US9309204B2 (en) | 2012-05-17 | 2016-04-12 | Array Biopharma Inc. | Process for making hydroxylated cyclopentylpyrimidine compounds |
US9315471B2 (en) | 2012-05-17 | 2016-04-19 | Genetech, Inc. | Process of making hydroxylated cyclopentapyrimidine compounds and salts thereof |
US9416110B2 (en) | 2012-05-17 | 2016-08-16 | Array Biopharma Inc. | Process for making hydroxylated cyclopentylpyrimidine compounds |
US9505725B2 (en) | 2012-05-17 | 2016-11-29 | Genentech, Inc. | Crystalline and mesomorphous forms of an AKT inhibiting pyrimidinyl-cyclopentane compound, compositions and methods thereof |
US9676730B2 (en) | 2012-05-17 | 2017-06-13 | Array Biopharma Inc. | Process for making hydroxylated cyclopentylpyrimidine compounds |
US9790190B2 (en) | 2012-05-17 | 2017-10-17 | Array Biopharma Inc. | Process for making hydroxylated cyclopentylpyrimidine compounds |
US9452990B2 (en) | 2012-06-20 | 2016-09-27 | Novartis Ag | Complement pathway modulators and uses thereof |
Also Published As
Publication number | Publication date |
---|---|
WO2000052134A3 (en) | 2001-07-05 |
AU3386600A (en) | 2000-09-21 |
JP2003524618A (en) | 2003-08-19 |
EP1158982A4 (en) | 2002-06-12 |
EP1158982A2 (en) | 2001-12-05 |
CA2363169A1 (en) | 2000-09-08 |
US6376496B1 (en) | 2002-04-23 |
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